Back to Search Start Over

Vascular dysfunction and arterial hypertension in experimental celiac disease are mediated by gut-derived inflammation and oxidative stress

Authors :
Karin Keppeler
Aline Pesi
Simon Lange
Johanna Helmstädter
Lea Strohm
Henning Ubbens
Marin Kuntić
Ivana Kuntić
Dominika Mihaliková
Ksenija Vujačić-Mirski
Alexandra Rosenberger
Leonie Küster
Charlotte Frank
Matthias Oelze
Stefanie Finger
Agnieszka Zakrzewska
Elena Verdu
Johannes Wild
Susanne Karbach
Philip Wenzel
Philipp Wild
David Leistner
Thomas Münzel
Andreas Daiber
Detlef Schuppan
Sebastian Steven
Source :
Redox Biology, Vol 70, Iss , Pp 103071- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Aims: We examined the cardiovascular effects of celiac disease (CeD) in a humanized mouse model, with a focus on vascular inflammation, endothelial dysfunction, and oxidative stress. Methods and results: NOD.DQ8 mice genetically predisposed to CeD were subjected to a diet regime and oral gavage to induce the disease (gluten group vs. control). We tested vascular function, confirmed disease indicators, and evaluated inflammation and oxidative stress in various tissues. Plasma proteome profiling was also performed.CeD markers were confirmed in the gluten group, indicating increased blood pressure and impaired vascular relaxation. Pro-inflammatory genes were upregulated in this group, with increased CD11b+ myeloid cell infiltration and oxidative stress parameters observed in aortic and heart tissue. However, heart function remained unaffected. Plasma proteomics suggested the cytokine interleukin-17A (IL-17A) as a link between gut and vascular inflammation. Cardiovascular complications were reversed by adopting a gluten-free diet. Conclusion: Our study sheds light in the heightened cardiovascular risk associated with active CeD, revealing a gut-to-cardiovascular inflammatory axis potentially mediated by immune cell infiltration and IL-17A. These findings augment our understanding of the link between CeD and cardiovascular disease providing clinically relevant insight into the underlying mechanism. Furthermore, our discovery that cardiovascular complications can be reversed by a gluten-free diet underscores a critical role for dietary interventions in mitigating cardiovascular risks associated with CeD.

Details

Language :
English
ISSN :
22132317
Volume :
70
Issue :
103071-
Database :
Directory of Open Access Journals
Journal :
Redox Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.904e326b45ef4db18421f8a462304e01
Document Type :
article
Full Text :
https://doi.org/10.1016/j.redox.2024.103071